Combination nonviral cytokine gene therapy for head and neck cancer

Objective: To establish the feasibility and efficacy of combination nonviral murine interferon-alpha (mIFN-alpha) and murine interleukin-2 (mIL-2) or murine interleukin-la (mIL-12) gene therapy for head and neck squamous cell carcinoma in a murine model. Study Design: Randomized controlled studies in a murine head and neck cancer model were performed to assess antitumor responses, secondary cytokine expression, and both natural killer (NK) cell and cytolytic T-cell (CTL) activity, Methods: Tumors were established in the floor of mouth in C3H/HeJ immunocompetent mice. Established tumors were directly injected with polymer-formulated murine interferon-alpha (mIFN-alpha), Lipid-formulated mIL-2, and polymer-formulated mIL-12 alone or in combination. Primary and secondary cytokine expression, NK cell activity, and CTL activity were assayed. Results: The use of mIFN-alpha gene therapy in combination with either mIL-2 or mIL-12 resulted in significant antitumor effects as compared with each of the single cytokine and control treatment groups (P = .002), Increased levels of NK cell activity and tumor specific CD8(+) cytotoxic T-lymphocyte activity were found in the combination mIFN-alpha and mIL-2 or mIL-12 groups. Augmented immune responses correlated with clinical antitumor effects. Conclusions: The present study demonstrates that mIL-2 or mIL-12 augments tumor inhibition from mIFN-alpha and increases activation of Mt and CD8(+) T cells. These data support further investigation of polymer and lipid mediated delivery of cytokine genes for head and neck cancer.